遗传易感性导致良性前列腺特异性抗原水平升高的临床后果。

Clinical consequences of a genetic predisposition toward higher benign prostate-specific antigen levels.

机构信息

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

出版信息

EBioMedicine. 2023 Nov;97:104838. doi: 10.1016/j.ebiom.2023.104838. Epub 2023 Oct 20.

DOI:10.1016/j.ebiom.2023.104838

PMID:37865044

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10597757/

Abstract

BACKGROUND

Prostate-specific antigen (PSA) levels are influenced by genetic variation unrelated to prostate cancer risk. Whether a genetic predisposition to a higher PSA level predisposes to a diagnostic work-up for prostate cancer is not known.

METHODS

Participants were 3110 men of African and European ancestries ages 45-70, without prostate cancer and with a baseline PSA < 4 ng/mL, undergoing routine clinical PSA screening. The exposure was a polygenic score (PGS) comprising 111 single nucleotide polymorphisms associated with PSA level, but not prostate cancer. We tested whether the PGS was associated with a: 1) PSA value > 4 ng/mL, 2) International Classification of Diseases (ICD) code for an elevated PSA, 3) encounter with a urologist, or 4) prostate biopsy. Multivariable Cox proportional hazards models were adjusted for age and genetic principal components. Analyses were stratified by age (45-59 years, and 60-70 years old). Association estimates are per standard deviation change in the PGS.

FINDINGS

The median age was 56.6 years, and 2118 (68%) participants were 45-59 years. The median (IQR) baseline PSA level was 1.0 (0.6-1.7) ng/mL. Among men ages 45-59, the PGS was associated with a PSA > 4 (hazard ratio [HR] = 1.35 [95% CI, 1.17-1.57], p = 4.5 × 10), an ICD code for elevated PSA (HR = 1.30 [1.12-1.52], p = 8.0 × 10), a urological evaluation (HR = 1.34 [1.14-1.57], p = 4.8 × 10), and undergoing a prostate biopsy (HR = 1.35 [1.11-1.64], p = 0.002). Among men ages 60-70, association effect sizes were smaller and not significant.

INTERPRETATION

A predisposition toward higher PSA levels was associated with clinical evaluations of an elevated PSA among men ages 45-59 years.

FUNDING

National Institutes of Health (NIH).

摘要

背景

前列腺特异性抗原（PSA）水平受到与前列腺癌风险无关的遗传变异的影响。一个人是否具有更高 PSA 水平的遗传倾向是否会导致对前列腺癌进行诊断性检查尚不清楚。

方法

参与者为 3110 名年龄在 45-70 岁之间的非洲裔和欧洲裔男性，没有前列腺癌，且基线 PSA<4ng/ml，正在接受常规临床 PSA 筛查。暴露因素是一种多基因评分（PGS），由 111 个与 PSA 水平相关但与前列腺癌无关的单核苷酸多态性组成。我们检测了 PGS 是否与以下情况相关：1）PSA 值>4ng/ml；2）国际疾病分类（ICD）编码的 PSA 升高；3）与泌尿科医生的接触；4）前列腺活检。多变量 Cox 比例风险模型根据年龄和遗传主成分进行了调整。分析按年龄（45-59 岁和 60-70 岁）进行分层。关联估计值是 PGS 标准偏差变化的每一项。

结果

中位年龄为 56.6 岁，2118 名（68%）参与者年龄在 45-59 岁。中位（IQR）基线 PSA 水平为 1.0（0.6-1.7）ng/ml。在 45-59 岁的男性中，PGS 与 PSA>4（危险比[HR]为 1.35[95%CI，1.17-1.57]，p=4.5×10）、PSA 升高的 ICD 编码（HR 为 1.30[1.12-1.52]，p=8.0×10）、泌尿科评估（HR 为 1.34[1.14-1.57]，p=4.8×10）和前列腺活检（HR 为 1.35[1.11-1.64]，p=0.002）相关。在 60-70 岁的男性中，关联效应大小较小且不显著。